What causes Syndrome of Inappropriate Antidiuretic Hormone (SIADH)?

From the Guidelines

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is primarily caused by excessive release of antidiuretic hormone (ADH) from various sources, including the pituitary gland and non-pituitary sources, leading to water retention and hyponatremia. The most common causes of SIADH include:

• Certain medications, such as antidepressants (e.g., SSRIs), antipsychotics, carbamazepine, and chemotherapy agents
• Central nervous system disorders, including stroke, hemorrhage, tumors, or infections like meningitis
• Pulmonary diseases, especially pneumonia, tuberculosis, and small cell lung cancer
• Various malignancies, particularly small cell lung cancer, pancreatic cancer, and lymphomas
• Other causes, such as post-surgical states, HIV infection, and pain or stress 1. The excessive ADH causes the kidneys to reabsorb more water than necessary, diluting the sodium concentration in the blood, resulting in hyponatremia with concentrated urine despite low serum osmolality, which distinguishes SIADH from other causes of hyponatremia. Treatment of SIADH depends on identifying and addressing the underlying cause while managing the hyponatremia through fluid restriction, salt supplementation, or in severe cases, medications like tolvaptan that block ADH effects on the kidneys. It is essential to assess alternative causes of hyponatremia, such as hypothyroidism and hypoaldosteronism, and to consider the use of vasopressin antagonists, like conivaptan and tolvaptan, in the short term to improve serum sodium concentration in hypervolemic, hyponatremic states 1.

From the Research

Causes of SIADH

The Syndrome of Inappropriate Antidiuretic Hormone (SIADH) can be caused by various factors, including:

• Traumatic brain injury (TBI) 2, which can lead to damage to the pituitary stalk or posterior pituitary, resulting in inappropriate non-osmotic hypersecretion of ADH.
• Medications, such as:
  • Selective serotonin reuptake inhibitors (SSRIs) 3, 4, 5, which can disrupt the action of antidiuretic hormone in the body.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) 3, which can also contribute to the development of SIADH.
  • Anticonvulsants, antipsychotic agents, cytotoxic agents, and pain medications 4, which have been implicated in drug-associated SIADH.
• Malignancies, such as:
  • Small cell lung cancer (SCLC) 6, which is well-known to be associated with SIADH.
  • Non-small cell lung cancer (NSCLC) 6, which has been rarely reported to be associated with SIADH.
• Other factors, such as:
  • Meninigo-encephalitis 2, which can complicate SIADH.
  • Post-traumatic amnesia and mild cognitive deficits 2, which can occur after TBI and contribute to the development of SIADH.

Risk Factors

Certain populations are at higher risk of developing SIADH, including:

• Elderly individuals 3, 5, who may be more susceptible to the effects of medications and underlying medical conditions.
• Patients taking diuretics 5, who may be at increased risk of developing hyponatremia.
• Patients with a history of asymptomatic chronic hyponatremia 3, who may be more likely to develop symptomatic hyponatremia.